Cytotoxicity and Mode of Action of Four Naturally Occuring Flavonoids from the GenusDorstenia: Gancaonin Q, 4-Hydroxylonchocarpin, 6-Prenylapigenin, and 6,8-Diprenyleriodictyol

Abstract

Several flavonoid-like compounds were found to possess good antiproliferative properties. Herein, we examined the ability of four naturally occuring and biologically active flavonoids from the genus Dorstenia, gancaonin Q (1), 6-prenylapigenin (2), 6,8-diprenyleriodictyol (3), and 4-hydroxylonchocarpin ( 4), to inhibit the proliferation of a panel of fourteen cancer cell lines including leukemia and solid cancer cells, as well as AML12 normal hepatocytes. The study was extended to the analysis of cell cycle distribution, apoptosis induction, and caspase 3/7 activity and the antiangiogenic properties of the four compounds. The results of the cytotoxicity assays showed that more than 50 % inhibition of proliferation was obtained with compound 1 on all the fourteen studied cancer cell lines, with IC (50) values below 20 µg/mL. Compounds 2, 4, and 3 showed selective activity, with IC (50) values below 20 µg/mL being noted on 57.15 %, 71.42 %, and 85.71 % of the fourteen cancer cell lines, respectively. None of the compounds exhibited more than 50 % inhibition against AML12 normal hepatocytes cells at 20 µg/mL. IC (50) values below or around 4 µg/mL were recorded on 28.57 % of the tested cell lines for both compound 1 and 4 and 21.43 % for compound 3, which appeared to be the best cytotoxic compounds. This study indicates that caspase 3/7 activation is one of the modes of induction of apoptosis for compounds 1, 3, and 4 in CCRF-CEM cells. The results of the antiangiogenic assay indicated that compounds 1, 3, and 4 were also able to inhibit the growth of blood capillaries on the chorioallantoic membrane of quail eggs, the best effect being noted for compound 4 (54.1 % inhibition). The results of the present work provide evidence of the cytotoxic potential of the four studied flavonoids and supportive data for further investigations.

Isolation of Flavonoids from Deguelia duckeana and Their Effect on Cellular Viability, AMPK, eEF2, eIF2 and eIF4E

“…Reactive oxygen radicals are harmful to biomembranes, but can additionally play a role as mediators in different signaling pathways [1,2]. Depending on their structural features, flavonoids such as prenylated flavones or chalcones, can also be involved in cytotoxic processes [3,4].…”

Cytotoxic flavonoids and isoflavonoids from Erythrina sigmoidea towards multi-factorial drug resistant cancer cells

“…1) [7]. We previously reported the isolation and the cytotoxicity of 8 identified from the roots of Erythrina senegalensis [8] and it was not more studied herein. Flavonoids 1, 3 and 6 pterocarpan isoflavonoids (4 and 7) as well as the other isoflavonoids 2, 4 and 5 were tested for their cytotoxicity towards drug sensitive and resistant cancer cells lines and further mechanistic studies were performed on the most active samples.…”

“…Several phytochemicals isolated from the Cameroonian medicinal plants were previously reported for their cytotoxicty against cancer cells. Some of them include flavonoids from Polygonum limbatum [9], Dorstenia species [10] and isoflavonoids from Erythrina excelsa and Erythrina senegalensis [8]. Also, the bioactivity of some of the compounds reported herein such as abyssinone IV [11], atalantoflavone [12], bidwillon A [13] and neocyclomorusin [14] was reported.…”

“…The rational of the present study comes to the fact that several flavonoids, isoflavonoids and mostly pterocarpan isoflavonoids were previously isolated from Erythrina sigmoidea Hua (Leguminosae) [7] and that such classes of compounds isolated from Erythrina species [8] showed interresting cytotoxic effects. In our continous search of antiproliferative phytochemicals from Cameroonian medicinal plants, we aimed this study at investigating the cytotoxicity of flavonoids and isoflavonoids isolated from Erythrina sigmoidea Hua (Leguminosae), namely abyssinone IV (1), sigmoidin I (2), atalantoflavone (3), sophorapterocarpan A (4), bidwillon A (5), neocyclomorusin (6), 6α-hydroxyphaseollidin (7) and neobavaisoflavone (8), with emphasis on multi-factorial drug resistant cancer cell lines. The effects of 1, 2, 4 and 7 were also analyzed regarding cell cycle arrest, apoptosis, generation of reactive oxygen species (ROS), caspases activation, and breakdown of mitochondrial membrane potential.…”

Review of the Chemistry and Pharmacology of 7-Methyljugulone

“…This clearly shows that this compounds can be explored more as potential drug against some pathogenic fungi and bacteria. In the US NCI screening program, a compound is generally considered to have in vitro cytotoxic activity, if the IC 50 value following incubation between 48 and 72 h, is less than 4 µg/ml or 10 μM 30 .…”